@article{MTMT:30703953,
	title = {Limited evolutionary conservation of the phenotypic effects of antibiotic resistance mutations},
	url = {https://m2.mtmt.hu/api/publication/30703953},
	author = {Apjok, Gábor and Boross, Gábor and Nyerges, Ákos and Fekete, Gergely and Lázár, Viktória and Papp, Balázs and Pál, Csaba and Csörgő, Bálint},
	doi = {10.1093/molbev/msz109},
	journal-iso = {MOL BIOL EVOL},
	journal = {MOLECULAR BIOLOGY AND EVOLUTION},
	volume = {36},
	unique-id = {30703953},
	issn = {0737-4038},
	year = {2019},
	eissn = {1537-1719},
	pages = {1601-1611},
	orcid-numbers = {Boross, Gábor/0000-0002-7208-5678; Nyerges, Ákos/0000-0002-1581-490X; Csörgő, Bálint/0000-0003-0397-6845}
}

@article{MTMT:3390047,
	title = {Directed evolution of multiple genomic loci allows the prediction of antibiotic resistance.},
	url = {https://m2.mtmt.hu/api/publication/3390047},
	author = {Nyerges, Ákos and Csörgő, Bálint and Draskovits, Gábor and Kintses, Bálint and Szili, Petra and Ferenc, Györgyi and Révész, Tamás and Ari, Eszter and Nagy, István and Bálint, Balázs and Vásárhelyi, Bálint Márk and Bihari, Péter and Számel, Mónika and Balogh, Dávid and Papp, Henrietta and Kalapis, Dorottya and Papp, Balázs and Pál, Csaba},
	doi = {10.1073/pnas.1801646115},
	journal-iso = {P NATL ACAD SCI USA},
	journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
	volume = {115},
	unique-id = {3390047},
	issn = {0027-8424},
	abstract = {Antibiotic development is frequently plagued by the rapid emergence of drug resistance. However, assessing the risk of resistance development in the preclinical stage is difficult. Standard laboratory evolution approaches explore only a small fraction of the sequence space and fail to identify exceedingly rare resistance mutations and combinations thereof. Therefore, new rapid and exhaustive methods are needed to accurately assess the potential of resistance evolution and uncover the underlying mutational mechanisms. Here, we introduce directed evolution with random genomic mutations (DIvERGE), a method that allows an up to million-fold increase in mutation rate along the full lengths of multiple predefined loci in a range of bacterial species. In a single day, DIvERGE generated specific mutation combinations, yielding clinically significant resistance against trimethoprim and ciprofloxacin. Many of these mutations have remained previously undetected or provide resistance in a species-specific manner. These results indicate pathogen-specific resistance mechanisms and the necessity of future narrow-spectrum antibacterial treatments. In contrast to prior claims, we detected the rapid emergence of resistance against gepotidacin, a novel antibiotic currently in clinical trials. Based on these properties, DIvERGE could be applicable to identify less resistance-prone antibiotics at an early stage of drug development. Finally, we discuss potential future applications of DIvERGE in synthetic and evolutionary biology.},
	keywords = {ESCHERICHIA-COLI; DRUG-RESISTANCE; URINARY-TRACT-INFECTIONS; QUINOLONE RESISTANCE; ANTIMICROBIAL RESISTANCE; Synthetic biology; RANDOM MUTAGENESIS; Homologous recombination; DIRECTED EVOLUTION; GENE MODIFICATION; COLI DIHYDROFOLATE-REDUCTASE; STRANDED-DNA OLIGONUCLEOTIDES; multiplex automated genome engineering; high-throughput mutagenesis},
	year = {2018},
	eissn = {1091-6490},
	pages = {E5726-E5735},
	orcid-numbers = {Nyerges, Ákos/0000-0002-1581-490X; Csörgő, Bálint/0000-0003-0397-6845; Ferenc, Györgyi/0000-0002-3456-319X; Ari, Eszter/0000-0001-7774-1067; Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Papp, Henrietta/0000-0003-3887-5657}
}

@article{MTMT:2998416,
	title = {Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics},
	url = {https://m2.mtmt.hu/api/publication/2998416},
	author = {Colin, P-Y and Kintses, Bálint and Gielen, F and Miton, CM and Fischer, G and Mohamed, MF and Hyvönen, M and Morgavi, DP and Janssen, DB and Hollfelder, F},
	doi = {10.1038/ncomms10008},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {6},
	unique-id = {2998416},
	issn = {2041-1723},
	abstract = {Unculturable bacterial communities provide a rich source of biocatalysts, but their experimental discovery by functional metagenomics is difficult, because the odds are stacked against the experimentor. Here we demonstrate functional screening of a million-membered metagenomic library in microfluidic picolitre droplet compartments. Using bait substrates, new hydrolases for sulfate monoesters and phosphotriesters were identified, mostly based on promiscuous activities presumed not to be under selection pressure. Spanning three protein superfamilies, these break new ground in sequence space: promiscuity now connects enzymes with only distantly related sequences. Most hits could not have been predicted by sequence analysis, because the desired activities have never been ascribed to similar sequences, showing how this approach complements bioinformatic harvesting of metagenomic sequencing data. Functional screening of a library of unprecedented size with excellent assay sensitivity has been instrumental in identifying rare genes constituting catalytically versatile hubs in sequence space as potential starting points for the acquisition of new functions.},
	year = {2015},
	eissn = {2041-1723}
}